Abstract
Objective: Mesenchymal stem cells (MSCs) are isolated from various human tissues and used for therapy, in which beneficial effects are attributed mainly to mesenchymal stem cell-derived extracellular vesicles (MSC-EVs). Whereas MSCs of diverse tissue types share cardinal stem cell features, it is becoming evident that MSCs of each tissue type possess unique properties as well. For designing efficient stem cellbased therapies, it is crucial to understand the unique properties associated with MSCs and MSC-EVs of each tissue type. Such unique properties can be analyzed through transcriptomic approaches using comprehensive gene expression databases and sophisticated analytical tools. Here, we comparatively studied the transcriptomes in MSC-EVs of dental pulp and adipose tissue. Additionally, the transcriptomes of MSC-EVs were compared with the cellular transcriptomes of MSCs for the same tissue types. Methods: MSCs were cultured from human dental pulp and adipose tissue specimens. Conditioned culture media were collected to prepare MSC-EVs, from which RNAs were isolated and subjected to next-generation sequencing for transcriptomic analysis. Gene expression signatures in MSC-EVs of each tissue type were investigated using gene set analysis. Results: MSC-EVs obtained from dental pulp-derived MSCs showed distinct transcriptomic signatures of neurogenesis and neural retina development while MSC-EVs of adipose tissue-derived MSCs showed signatures of mitochondrial activity and skeletal system development. The transcriptomes of MSC-EVs resembled the cellular transcriptomes of MSCs, and the genes associated with neurogenesis were highly expressed in both MSCs and MSC-EVs of dental pulp. Adipose tissue-derived MSCs and MSC-EVs highly expressed genes associated with angiogenesis, hair growth, and dermal matrices. Conclusion: The clear and distinct signatures of neurogenesis and neural retina development in dental pulp-derived MSC-EVs imply neurodegenerative disorders and retinal diseases as putative therapeutic targets. In contrast, the transcripts in adipose tissue-derived MSC-EVs could be useful in rejuvenating the skin and musculoskeletal system. Further insights into MSC-EVs of divergent tissue types may expand the list of potential therapeutic targets.
Highlights
Mesenchymal stem cells (MSCs) are isolated from divergent adult tissues for clinical applications to demonstrate promising therapeutic potentials[1, 2]
The transcriptomes of mesenchymal stem cell-derived extracellular vesicles (MSC-extracellular vesicles (EVs)) resembled the cellular transcriptomes of MSCs, and the genes associated with neurogenesis were highly expressed in both MSCs and MSC-EVs of dental pulp
Adipose tissue-derived MSCs and MSC-EVs highly expressed genes associated with angiogenesis, hair growth, and dermal matrices
Summary
MSCs are isolated from divergent adult tissues for clinical applications to demonstrate promising therapeutic potentials[1, 2]. Many studies suggest that MSCs exert beneficial effects via secreted factors including extracellular vesicles (EVs)[3, 4]. Whereas MSCs from various tissues share common stem cell markers and biological behaviors, they appear to possess unique properties depending on the tissue types they originated from[5, 6]. Diversity of MSCs from different tissue types may result in various efficacies of MSCs in treating a disease of interest[7, 8], and the MSCs with the highest efficacy should be chosen for successful stem cell-based therapies[9]. Considering the pivotal role of EVs in exerting therapeutic effects of MSCs, it is crucial to understand the unique properties of MSC-EVs of various tissue types so that MSC-EVs with the most desirable properties are chosen for the therapy. MSCs and MSCEVs can be characterized by analyzing proteins, microRNAs and mRNAs
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